Multiscale Monte Carlo simulations for dosimetry in x-ray breast imaging: Part II - Microscopic scales.

BACKGROUND: Although the benefits of breast screening and early diagnosis are known for reducing breast cancer mortality rates, the effects and risks of low radiation doses to the cells in the breast are still ongoing topics of study. PURPOSE: To study specific energy distributions ( f ( z , D g ) $f(z,D_{g})$ ) in cytoplasm and nuclei of cells corresponding to glandular tissue for different x-ray breast imaging modalities. METHODS: A cubic lattice (500 µm length side) containing 4064 spherical cells was irradiated with photons loaded from phase space files with varying glandular voxel doses ( D g $D_{g}$ ). Specific energy distributions were scored for nucleus and cytoplasm compartments using the PENELOPE (v. 2018) + penEasy (v. 2020) Monte Carlo (MC) code. The phase space files, generated in part I of this work, were obtained from MC simulations in a voxelized anthropomorphic phantom corresponding to glandular voxels for different breast imaging modalities, including digital mammography (DM), digital breast tomosynthesis (DBT), contrast enhanced digital mammography (CEDM) and breast CT (BCT). RESULTS: In general, the average specific energy in nuclei is higher than the respective glandular dose scored in the same region, by up to 10%. The specific energy distributions for nucleus and cytoplasm are directly related to the magnitude of the glandular dose in the voxel ( D g $D_{g}$ ), with little dependence on the spatial location. For similar D g $D_{g}$ values, f ( z , D g ) $f(z,D_{g})$ for nuclei is different between DM/DBT and CEDM/BCT, indicating that distinct x-ray spectra play significant roles in f ( z , D g ) $f(z,D_{g})$ . In addition, this behavior is also present when the specific energy distribution ( F g ( z ) $F_{g}(z)$ ) is considered taking into account the GDD in the breast. CONCLUSIONS: Microdosimetry studies are complementary to the traditional macroscopic breast dosimetry based on the mean glandular dose (MGD). For the same MGD, the specific energy distribution in glandular tissue varies between breast imaging modalities, indicating that this effect could be considered for studying the risks of exposing the breast to ionizing radiation.

Multiscale Monte Carlo simulations for dosimetry in x-ray breast imaging: Part I - Macroscopic scales.

BACKGROUND: X-ray breast imaging modalities are commonly employed for breast cancer detection, from screening programs to diagnosis. Thus, dosimetry studies are important for quality control and risk estimation since ionizing radiation is used. PURPOSE: To perform multiscale dosimetry assessments for different breast imaging modalities and for a variety of breast sizes and compositions. The first part of our study is focused on macroscopic scales (down to millimeters). METHODS: Nine anthropomorphic breast phantoms with a voxel resolution of 0.5 mm were computationally generated using the BreastPhantom software, representing three breast sizes with three distinct values of volume glandular fraction (VGF) for each size. Four breast imaging modalities were studied: digital mammography (DM), contrast-enhanced digital mammography (CEDM), digital breast tomosynthesis (DBT) and dedicated breast computed tomography (BCT). Additionally, the impact of tissue elemental compositions from two databases were compared. Monte Carlo (MC) simulations were performed with the MC-GPU code to obtain the 3D glandular dose distribution (GDD) for each case considered with the mean glandular dose (MGD) fixed at 4 mGy (to facilitate comparisons). RESULTS: The GDD within the breast is more uniform for CEDM and BCT compared to DM and DBT. For large breasts and high VGF, the ratio between the minimum/maximum glandular dose to MGD is 0.12/4.02 for DM and 0.46/1.77 for BCT; the corresponding results for a small breast and low VGF are 0.35/1.98 (DM) and 0.63/1.42 (BCT). The elemental compositions of skin, adipose and glandular tissue have a considerable impact on the MGD, with variations up to 30% compared to the baseline. The inclusion of tissues other than glandular and adipose within the breast has a minor impact on MGD, with differences below 2%. Variations in the final compressed breast thickness alter the shape of the GDD, with a higher compression resulting in a more uniform GDD. CONCLUSIONS: For a constant MGD, the GDD varies with imaging modality and breast compression. Elemental tissue compositions are an important factor for obtaining MGD values, being a source of systematic uncertainties in MC simulations and, consequently, in breast dosimetry.

Generation and comparison of 3D dosimetric reference datasets for COMS eye plaque brachytherapy using model-based dose calculations.

PURPOSE: A joint Working Group of the American Association of Physicists in Medicine (AAPM), the European Society for Radiotherapy and Oncology (ESTRO), and the Australasian Brachytherapy Group (ABG) was created to aid in the transition from the AAPM TG-43 dose calculation formalism, the current standard, to model-based dose calculations. This work establishes the first test cases for low-energy photon-emitting brachytherapy using model-based dose calculation algorithms (MBDCAs). ACQUISITION AND VALIDATION METHODS: Five test cases are developed: (1) a single model 6711 125 I brachytherapy seed in water, 13 seeds (2) individually and (3) in combination in water, (4) the full Collaborative Ocular Melanoma Study (COMS) 16 mm eye plaque in water, and (5) the full plaque in a realistic eye phantom. Calculations are done with four Monte Carlo (MC) codes and a research version of a commercial treatment planning system (TPS). For all test cases, local agreement of MC codes was within ∼2.5% and global agreement was ∼2% (4% for test case 5). MC agreement was within expected uncertainties. Local agreement of TPS with MC was within 5% for test case 1 and ∼20% for test cases 4 and 5, and global agreement was within 0.4% for test case 1 and 10% for test cases 4 and 5. DATA FORMAT AND USAGE NOTES: Dose distributions for each set of MC and TPS calculations are available online (https://doi.org/10.52519/00005) along with input files and all other information necessary to repeat the calculations. POTENTIAL APPLICATIONS: These data can be used to support commissioning of MBDCAs for low-energy brachytherapy as recommended by TGs 186 and 221 and AAPM Report 372. This work additionally lays out a sample framework for the development of test cases that can be extended to other applications beyond eye plaque brachytherapy.

Haralick texture feature analysis for characterization of specific energy and absorbed dose distributions across cellular to patient length scales.

Objective.To investigate an approach for quantitative characterization of the spatial distribution of dosimetric data by introducing Haralick texture feature analysis in this context.Approach.Monte Carlo simulations are used to generate 3D arrays of dosimetric data for 2 scenarios: (1) cell-scale microdosimetry: specific energy (energy imparted per unit mass) in cell-scale targets irradiated by photon spectra (125I,192Ir, 6 MV); (2) tumour-scale dosimetry: absorbed dose in voxels for idealized models of125I permanent implant prostate brachytherapy, considering 'TG186' (realistic tissues including 0% to 5% intraprostatic calcifications; interseed attenuation) and 'TG43' (water model, no interseed attenuation) conditions. Five prominent Haralick features (homogeneity, contrast, correlation, local homogeneity, entropy) are computed and trends are interpreted using fundamental radiation physics.Main results.In the cell-scale scenario, the Haralick measures quantify differences in 3D specific energy distributions due to source spectra. For example, contrast and entropy are highest for125I reflecting the large variations in specific energy in adjacent voxels (photoelectric interactions; relatively short range of electrons), while 6 MV has the highest homogeneity with smaller variations in specific energy between voxels (Compton scattering dominates; longer range of electrons). For the tumour-scale scenario, the Haralick measures quantify differences due to TG186/TG43 simulation conditions and the presence of calcifications. For example, as calcifications increase from 0% to 5%, contrast increases while correlation decreases, reflecting the large differences in absorbed dose in adjacent voxels (higher absorbed dose in voxels with calcification due to photoelectric interactions).Significance.Haralick texture analysis provides a quantitative method for the characterization of 3D dosimetric distributions across cellular to tumour length scales, with promising future applications including analyses of multiscale tissue models, patient-specific data, and comparison of treatment approaches.

Haralick texture analysis for microdosimetry: characterization of Monte Carlo generated 3D specific energy distributions.

Objective.Explore the application of Haralick textural analysis to 3D distributions of specific energy (energy imparted per unit mass) scored in cell-scale targets considering varying mean specific energy (absorbed dose), target volume, and incident spectrum.Approach.Monte Carlo simulations are used to generate specific energy distributions in cell-scale water voxels ((1µm)3-(15µm)3) irradiated by photon sources (mean energies: 0.02-2 MeV) to varying mean specific energies (10-400 mGy). Five Haralick features (homogeneity, contrast, entropy, correlation, local homogeneity) are calculated using an implementation of Haralick analysis designed to reduce sensitivity to grey level quantization and are interpreted using fundamental radiation physics.Main results.Haralick measures quantify differences in 3D specific energy distributions observed with varying voxel volume, absorbed dose magnitude, and source spectrum. For example, specific energy distributions in small (1-3µm) voxels with low magnitudes of absorbed dose (10 mGy) have relatively high measures of homogeneity and local homogeneity and relatively low measures of contrast and entropy (all relative to measures for larger voxels), reflecting the many voxels with zero specific energy in an otherwise sporadic distribution. With increasing target size, energy is shared across more target voxels, and trends in Haralick measures, such as decreasing homogeneity and increasing contrast and entropy, reflect characteristics of each 3D specific energy distribution. Specific energy distributions for sources of differing mean energy are characterized by Haralick measures, e.g. contrast generally decreases with increasing source energy, correlation and homogeneity are often (not always) higher for higher energy sources.Significance.Haralick texture analysis successfully quantifies spatial trends in 3D specific energy distributions characteristic of radiation source, target size, and absorbed dose magnitude, thus offering new avenues to quantify microdosimetric data beyond first order histogram features. Promising future directions include investigations of multiscale tissue models, targeted radiation therapy techniques, and biological response to radiation.

Multiscale Monte Carlo simulations of gold nanoparticle dose-enhanced radiotherapy I: Cellular dose enhancement in microscopic models.

BACKGROUND: The introduction of Gold NanoParticles (GNPs) in radiotherapy treatments necessitates considerations such as GNP size, location, and quantity, as well as patient geometry and beam quality. Physics considerations span length scales across many orders of magnitude (nanometer-to-centimeter), presenting challenges that often limit the scope of dosimetric studies to either micro- or macroscopic scales. PURPOSE: To investigate GNP dose-enhanced radiation Therapy (GNPT) through Monte Carlo (MC) simulations that bridge micro-to-macroscopic scales. The work is presented in two parts, with Part I (this work) investigating accurate and efficient MC modeling at the single cell level to calculate nucleus and cytoplasm Dose Enhancement Factors (n,cDEFs), considering a broad parameter space including GNP concentration, GNP intracellular distribution, cell size, and incident photon energy. Part II then evaluates cell dose enhancement factors across macroscopic (tumor) length scales. METHODS: Different methods of modeling gold within cells are compared, from a contiguous volume of either pure gold or gold-tissue mixture to discrete GNPs in a hexagonal close-packed lattice. MC simulations with EGSnrc are performed to calculate n,cDEF for a cell with radius r cell = 7.35 $r_{\rm cell}=7.35$  µm and nucleus r nuc = 5 $r_{\rm nuc} = 5$  µm considering 10 to 370 keV incident photons, gold concentrations from 4 to 24 mgAu /gtissue , and three different GNP configurations within the cell: GNPs distributed around the surface of the nucleus (perinuclear) or GNPs packed into one (or four) endosome(s). Select simulations are extended to cells with different cell (and nucleus) sizes: 5 µm (2, 3, and 4 µm), 7.35 µm (4 and 6 µm), and 10 µm (7, 8, and 9 µm). RESULTS: n,cDEFs are sensitive to the method of modeling gold in the cell, with differences of up to 17% observed; the hexagonal lattice of GNPs is chosen (as the most realistic model) for all subsequent simulations. Across cell/nucleus radii, source energies, and gold concentrations, both nDEF and cDEF are highest for GNPs in the perinuclear configuration, compared with GNPs in one (or four) endosome(s). Across all simulations of the (rcell , rnuc ) = (7.35, 5) µm cell, nDEFs and cDEFs range from unity to 6.83 and 3.87, respectively. Including different cell sizes, nDEFs and cDEFs as high as 21.5 and 5.5, respectively, are observed. Both nDEF and cDEF are maximized at photon energies above the K- or L-edges of gold by 10 to 20 keV. CONCLUSIONS: Considering 5000 unique simulation scenarios, this work comprehensively investigates many physics trends on DEFs at the cellular level, including demonstrating that cellular DEFs are sensitive to gold modeling approach, intracellular GNP configuration, cell/nucleus size, gold concentration, and incident source energy. These data should prove especially useful in research as well as treatment planning, allowing one to optimize or estimate DEF using not only GNP uptake, but also account for average tumor cell size, incident photon energy, and intracellular configuration of GNPs. Part II will expand the investigation, taking the Part I cell model and applying it in cm-scale phantoms.

Multiscale Monte Carlo simulations of gold nanoparticle dose-enhanced radiotherapy II. Cellular dose enhancement within macroscopic tumor models.

BACKGROUND: Gold NanoParticle (GNP) dose-enhanced radiation therapy (GNPT) requires consideration of physics across macro- to microscopic length scales, however, this presents computational challenges that have limited previous investigations. PURPOSE: To develop and apply multiscale Monte Carlo (MC) simulations to assess variations in nucleus and cytoplasm dose enhancement factors (n,cDEFs) over tumor-scale volumes. METHODS: The intrinsic variation of n,cDEFs (due to fluctuations in local gold concentration and cell/nucleus size variation) are estimated via MC modeling of varied cellular GNP uptake and cell/nucleus sizes. Then, the Heterogeneous MultiScale (HetMS) model is implemented in MC simulations by combining detailed models of populations of cells containing GNPs within simplified macroscopic tissue models to evaluate n,cDEFs. Simulations of tumors with spatially uniform gold concentrations (5, 10, or 20 mgAu /gtissue ) and spatially varying gold concentrations eluted from a point are performed to determine n,cDEFs as a function of distance from the source for 10 to 370 keV photons. All simulations are performed for three different intracellular GNP configurations: GNPs distributed on the surface of the nucleus (perinuclear) and GNPs packed into one or four endosome(s). RESULTS: Intrinsic variations in n,cDEFs can be substantial, for example, if GNP uptake and cell/nucleus radii are varied by 20%, variations of up to 52% in nDEF and 25% in cDEF are observed compared to the nominal values for uniform cell/nucleus size and GNP concentration. In HetMS models of macroscopic tumors, subunity n,cDEFs (i.e., dose decreases) can occur for low energies and high gold concentrations due to attenuation of primary photons through the gold-filled volumes, for example, n,cDEF<1 is observed 3 mm from a 20 keV source for the four endosome configuration. In HetMS simulations of tumors with spatially uniform gold concentrations, n,cDEFs decrease with depth into the tumor as photons are attenuated, with relative differences between GNP models remaining approximately constant with depth in the tumor. Similar initial n,cDEF decreases with radius are seen in the tumors with spatially varying gold concentrations, but the n,cDEFs for all of the GNP configurations converge to a single value for each energy as gold concentration reaches zero. CONCLUSIONS: The HetMS framework has been implemented for multiscale MC simulations of GNPT to compute n,cDEFs over tumor-scale volumes, with results demonstrating that cellular doses are highly sensitive to cell/nucleus size, GNP intracellular distribution, gold concentration, and cell position in tumor. This work demonstrates the importance of proper choice of computational model when simulating GNPT scenarios and the need to account for intrinsic variations in n,cDEFs due to variations in cell/nucleus size and gold concentration.

Update of the CLRP Monte Carlo TG-43 parameter database for high-energy brachytherapy sources.

PURPOSE: To update and extend version 2 of the Carleton Laboratory for Radiotherapy Physics (CLRP) TG-43 dosimetry database (CLRP_TG43v2) for high-energy (HE, ≥50 keV) brachytherapy sources (1 169 Yb, 23 192 Ir, 5 137 Cs, and 4 60 Co) using egs_brachy, an open-source EGSnrc application. A comprehensive dataset of TG-43 parameters is compiled, including detailed source descriptions, dose-rate constants, radial dose functions, 1D and 2D anisotropy functions, along-away dose-rate tables, Primary and Scatter Separated (PSS) dose tables, and mean photon energies escaping each source. The database also documents the source models which are freely distributed with egs_brachy. ACQUISITION AND VALIDATION METHODS: Datasets are calculated after a recoding of the source geometries using the egs++ geometry package and its egs_brachy extensions. Air kerma per history is calculated in a 10 × 10 × $\,{\times}\, 10\,{\times}\,$ 0.05 cm3 voxel located 100 cm from the source along the transverse axis and then corrected for the lateral and thickness dimensions of the scoring voxel to give the air kerma on the central axis at a point 100 cm from the source's mid-point. Full-scatter water phantoms with varying voxel resolutions in cylindrical coordinates are used for dose calculations. Most data (except for 60 Co) are based on the assumption of charged particle equilibrium and ignore the potentially large effects of electron transport very close to the source and dose from initial beta particles. These effects are evaluated for four representative sources. For validation, data are compared to those from CLRP_TG43v1 and published data. DATA FORMAT AND ACCESS: Data are available at https://physics.carleton.ca/clrp/egs_brachy/seed_database_v2 or http://doi.org/10.22215/clrp/tg43v2 including in Excel (.xlsx) spreadsheets, and are presented graphically in comparisons to previously published data for each source. POTENTIAL APPLICATIONS: The CLRP_TG43v2 database has applications in research, dosimetry, and brachytherapy planning. This comprehensive update provides the medical physics community with more precise and in some cases more accurate Monte Carlo (MC) TG-43 dose calculation parameters, as well as fully benchmarked and described source models which are distributed with egs_brachy.

A Monte Carlo dose recalculation pipeline for durable datasets: an I-125 LDR prostate brachytherapy use case.

Monte Carlo (MC) dose datasets are valuable for large-scale dosimetric studies. This work aims to build and validate a DICOM-compliant automated MC dose recalculation pipeline with an application to the production of I-125 low dose-rate prostate brachytherapy MC datasets. Built as a self-contained application, the recalculation pipeline ingested clinical DICOM-RT studies, reproduced the treatment into the Monte Carlo simulation, and outputted a traceable and durable dose distribution in the DICOM dose format. MC simulations with TG43-equivalent conditions using both TOPAS andegs_brachyMC codes were compared to TG43 calculations to validate the pipeline. The consistency of the pipeline when generating TG186 simulations was measured by comparing simulations made with both MC codes. Finally,egs_brachysimulations were run on a 240-patient cohort to simulate a large-scale application of the pipeline. Compared to line source TG43 calculations, simulations with both MC codes had more than 90% of voxels with a global difference under ±1%. Differences of 2.1% and less were seen in dosimetric indices when comparing TG186 simulations from both MC codes. The large-scale comparison ofegs_brachysimulations with treatment planning system dose calculation seen the same dose overestimation of TG43 calculations showed in previous studies. The MC dose recalculation pipeline built and validated against TG43 calculations in this work efficiently produced durable MC dose datasets. Since the dataset could reproduce previous dosimetric studies within 15 h at a rate of 20 cases per 25 min, the pipeline is a promising tool for future large-scale dosimetric studies.

A MC-based anthropomorphic test case for commissioning model-based dose calculation in interstitial breast 192-Ir HDR brachytherapy.

PURPOSE: To provide the first clinical test case for commissioning of 192 Ir brachytherapy model-based dose calculation algorithms (MBDCAs) according to the AAPM TG-186 report workflow. ACQUISITION AND VALIDATION METHODS: A computational patient phantom model was generated from a clinical multi-catheter 192 Ir HDR breast brachytherapy case. Regions of interest (ROIs) were contoured and digitized on the patient CT images and the model was written to a series of DICOM CT images using MATLAB. The model was imported into two commercial treatment planning systems (TPSs) currently incorporating an MBDCA. Identical treatment plans were prepared using a generic 192 Ir HDR source and the TG-43-based algorithm of each TPS. This was followed by dose to medium in medium calculations using the MBDCA option of each TPS. Monte Carlo (MC) simulation was performed in the model using three different codes and information parsed from the treatment plan exported in DICOM radiation therapy (RT) format. Results were found to agree within statistical uncertainty and the dataset with the lowest uncertainty was assigned as the reference MC dose distribution. DATA FORMAT AND USAGE NOTES: The dataset is available online at http://irochouston.mdanderson.org/rpc/BrachySeeds/BrachySeeds/index.html,https://doi.org/10.52519/00005. Files include the treatment plan for each TPS in DICOM RT format, reference MC dose data in RT Dose format, as well as a guide for database users and all files necessary to repeat the MC simulations. POTENTIAL APPLICATIONS: The dataset facilitates the commissioning of brachytherapy MBDCAs using TPS embedded tools and establishes a methodology for the development of future clinical test cases. It is also useful to non-MBDCA adopters for intercomparing MBDCAs and exploring their benefits and limitations, as well as to brachytherapy researchers in need of a dosimetric and/or a DICOM RT information parsing benchmark. Limitations include specificity in terms of radionuclide, source model, clinical scenario, and MBDCA version used for its preparation.

AAPM WGDCAB Report 372: A joint AAPM, ESTRO, ABG, and ABS report on commissioning of model-based dose calculation algorithms in brachytherapy.

The introduction of model-based dose calculation algorithms (MBDCAs) in brachytherapy provides an opportunity for a more accurate dose calculation and opens the possibility for novel, innovative treatment modalities. The joint AAPM, ESTRO, and ABG Task Group 186 (TG-186) report provided guidance to early adopters. However, the commissioning aspect of these algorithms was described only in general terms with no quantitative goals. This report, from the Working Group on Model-Based Dose Calculation Algorithms in Brachytherapy, introduced a field-tested approach to MBDCA commissioning. It is based on a set of well-characterized test cases for which reference Monte Carlo (MC) and vendor-specific MBDCA dose distributions are available in a Digital Imaging and Communications in Medicine-Radiotherapy (DICOM-RT) format to the clinical users. The key elements of the TG-186 commissioning workflow are now described in detail, and quantitative goals are provided. This approach leverages the well-known Brachytherapy Source Registry jointly managed by the AAPM and the Imaging and Radiation Oncology Core (IROC) Houston Quality Assurance Center (with associated links at ESTRO) to provide open access to test cases as well as step-by-step user guides. While the current report is limited to the two most widely commercially available MBDCAs and only for 192 Ir-based afterloading brachytherapy at this time, this report establishes a general framework that can easily be extended to other brachytherapy MBDCAs and brachytherapy sources. The AAPM, ESTRO, ABG, and ABS recommend that clinical medical physicists implement the workflow presented in this report to validate both the basic and the advanced dose calculation features of their commercial MBDCAs. Recommendations are also given to vendors to integrate advanced analysis tools into their brachytherapy treatment planning system to facilitate extensive dose comparisons. The use of the test cases for research and educational purposes is further encouraged.

Dosimetry of (125)I and (103)Pd COMS eye plaques for intraocular tumors: report of Task Group 129 by the AAPM and ABS.

Dosimetry of eye plaques for ocular tumors presents unique challenges in brachytherapy. The challenges in accurate dosimetry are in part related to the steep dose gradient in the tumor and critical structures that are within millimeters of radioactive sources. In most clinical applications, calculations of dose distributions around eye plaques assume a homogenous water medium and full scatter conditions. Recent Monte Carlo (MC)-based eye-plaque dosimetry simulations have demonstrated that the perturbation effects of heterogeneous materials in eye plaques, including the gold-alloy backing and Silastic insert, can be calculated with reasonable accuracy. Even additional levels of complexity introduced through the use of gold foil "seed-guides" and custom-designed plaques can be calculated accurately using modern MC techniques. Simulations accounting for the aforementioned complexities indicate dose discrepancies exceeding a factor of ten to selected critical structures compared to conventional dose calculations. Task Group 129 was formed to review the literature; re-examine the current dosimetry calculation formalism; and make recommendations for eye-plaque dosimetry, including evaluation of brachytherapy source dosimetry parameters and heterogeneity correction factors. A literature review identified modern assessments of dose calculations for Collaborative Ocular Melanoma Study (COMS) design plaques, including MC analyses and an intercomparison of treatment planning systems (TPS) detailing differences between homogeneous and heterogeneous plaque calculations using the American Association of Physicists in Medicine (AAPM) TG-43U1 brachytherapy dosimetry formalism and MC techniques. This review identified that a commonly used prescription dose of 85 Gy at 5 mm depth in homogeneous medium delivers about 75 Gy and 69 Gy at the same 5 mm depth for specific (125)I and (103)Pd sources, respectively, when accounting for COMS plaque heterogeneities. Thus, the adoption of heterogeneous dose calculation methods in clinical practice would result in dose differences >10% and warrant a careful evaluation of the corresponding changes in prescription doses. Doses to normal ocular structures vary with choice of radionuclide, plaque location, and prescription depth, such that further dosimetric evaluations of the adoption of MC-based dosimetry methods are needed. The AAPM and American Brachytherapy Society (ABS) recommend that clinical medical physicists should make concurrent estimates of heterogeneity-corrected delivered dose using the information in this report's tables to prepare for brachytherapy TPS that can account for material heterogeneities and for a transition to heterogeneity-corrected prescriptive goals. It is recommended that brachytherapy TPS vendors include material heterogeneity corrections in their systems and take steps to integrate planned plaque localization and image guidance. In the interim, before the availability of commercial MC-based brachytherapy TPS, it is recommended that clinical medical physicists use the line-source approximation in homogeneous water medium and the 2D AAPM TG-43U1 dosimetry formalism and brachytherapy source dosimetry parameter datasets for treatment planning calculations. Furthermore, this report includes quality management program recommendations for eye-plaque brachytherapy.

Report of the Task Group 186 on model-based dose calculation methods in brachytherapy beyond the TG-43 formalism: current status and recommendations for clinical implementation.

The charge of Task Group 186 (TG-186) is to provide guidance for early adopters of model-based dose calculation algorithms (MBDCAs) for brachytherapy (BT) dose calculations to ensure practice uniformity. Contrary to external beam radiotherapy, heterogeneity correction algorithms have only recently been made available to the BT community. Yet, BT dose calculation accuracy is highly dependent on scatter conditions and photoelectric effect cross-sections relative to water. In specific situations, differences between the current water-based BT dose calculation formalism (TG-43) and MBDCAs can lead to differences in calculated doses exceeding a factor of 10. MBDCAs raise three major issues that are not addressed by current guidance documents: (1) MBDCA calculated doses are sensitive to the dose specification medium, resulting in energy-dependent differences between dose calculated to water in a homogeneous water geometry (TG-43), dose calculated to the local medium in the heterogeneous medium, and the intermediate scenario of dose calculated to a small volume of water in the heterogeneous medium. (2) MBDCA doses are sensitive to voxel-by-voxel interaction cross sections. Neither conventional single-energy CT nor ICRU∕ICRP tissue composition compilations provide useful guidance for the task of assigning interaction cross sections to each voxel. (3) Since each patient-source-applicator combination is unique, having reference data for each possible combination to benchmark MBDCAs is an impractical strategy. Hence, a new commissioning process is required. TG-186 addresses in detail the above issues through the literature review and provides explicit recommendations based on the current state of knowledge. TG-43-based dose prescription and dose calculation remain in effect, with MBDCA dose reporting performed in parallel when available. In using MBDCAs, it is recommended that the radiation transport should be performed in the heterogeneous medium and, at minimum, the dose to the local medium be reported along with the TG-43 calculated doses. Assignments of voxel-by-voxel cross sections represent a particular challenge. Electron density information is readily extracted from CT imaging, but cannot be used to distinguish between different materials having the same density. Therefore, a recommendation is made to use a number of standardized materials to maintain uniformity across institutions. Sensitivity analysis shows that this recommendation offers increased accuracy over TG-43. MBDCA commissioning will share commonalities with current TG-43-based systems, but in addition there will be algorithm-specific tasks. Two levels of commissioning are recommended: reproducing TG-43 dose parameters and testing the advanced capabilities of MBDCAs. For validation of heterogeneity and scatter conditions, MBDCAs should mimic the 3D dose distributions from reference virtual geometries. Potential changes in BT dose prescriptions and MBDCA limitations are discussed. When data required for full MBDCA implementation are insufficient, interim recommendations are made and potential areas of research are identified. Application of TG-186 guidance should retain practice uniformity in transitioning from the TG-43 to the MBDCA approach.

Technical note: MC-GPU breast dosimetry validations with other Monte Carlo codes and phase space file implementation.

PURPOSE: To validate the MC-GPU Monte Carlo (MC) code for dosimetric studies in X-ray breast imaging modalities: mammography, digital breast tomosynthesis, contrast enhanced digital mammography, and breast-CT. Moreover, to implement and validate a phase space file generation routine. METHODS: The MC-GPU code (v. 1.5 DBT) was modified in order to generate phase space files and to be compatible with PENELOPE v. 2018 derived cross-section database. Simulations were performed with homogeneous and anthropomorphic breast phantoms for different breast imaging techniques. The glandular dose was computed for each case and compared with results from the PENELOPE (v. 2014) + penEasy (v. 2015) and egs _ brachy (EGSnrc) MC codes. Afterward, several phase space files were generated with MC-GPU and the scored photon spectra were compared between the codes. The phase space files generated in MC-GPU were used in PENELOPE and EGSnrc to calculate the glandular dose, and compared with the original dose scored in MC-GPU. RESULTS: MC-GPU showed good agreement with the other codes when calculating the glandular dose distribution for mammography, mean glandular dose for digital breast tomosynthesis, and normalized glandular dose for breast-CT. The latter case showed average/maximum relative differences of 2.3%/27%, respectively, compared to other literature works, with the larger differences observed at low energies (around 10 keV). The recorded photon spectra entering a voxel were similar (within statistical uncertainties) between the three MC codes. Finally, the reconstructed glandular dose in a voxel from a phase space file differs by less than 0.65%, with an average of 0.18%-0.22% between the different MC codes, agreement within approximately 2 σ statistical uncertainties. In some scenarios, the simulations performed in MC-GPU were from 20 up to 40 times faster than those performed by PENELOPE. CONCLUSIONS: The results indicate that MC-GPU code is suitable for breast dosimetric studies for different X-ray breast imaging modalities, with the advantage of a high performance derived from GPUs. The phase space file implementation was validated and is compatible with the IAEA standard, allowing multiscale MC simulations with a combination of CPU and GPU codes.

Fast beta-emitter Monte Carlo simulations and full patient dose calculations of targeted radionuclide therapy: introducing egs_mird.

BACKGROUND: Targeted radionuclide therapy (TRT) is a fast-growing field garnering much interest, with several clinical trials currently underway, that has a steady increase in development of treatment techniques. Unfortunately, within the field and many clinical trials, the dosimetry calculation techniques used remain relatively simple, often using a mix of S-value calculations and kernel convolutions. PURPOSE: The common TRT calculation techniques, although very quick, can often ignore important aspects of patient anatomy and radionuclide distribution, as well as the interplay there-in. This paper introduces egs_mird, a new Monte Carlo (MC) application built in EGSnrc which allows users to model full patient tissue and density (using clinical CT images) and radionuclide distribution (using clinical PET images) for fast and detailed dose TRT calculation. METHODS: The novel application egs_mird is introduced along with a general outline of the structure of egs_mird simulations. The general structure of the code, and the track-length (TL) estimator scoring implementation for variance reduction, is described. A new egs++ source class egs_internal_source, created to allow detailed patient-wide source distribution, and a modified version of egs_radionuclide_source, changed to be able to work with egs_internal_source, are also described. The new code is compared to other MC calculations of S-values kernels of 131 I, 90 Y, and 177 Lu in the literature, along with further self-validation using a histogram variant of the electron Fano test. Several full patient prostate 177 Lu TRT prostate cancer treatment simulations are performed using a single set of patient DICOM CT and [18 F]-DCFPyL PET data. RESULTS: Good agreement is found between S-value kernels calculated using egs_mird with egs_internal_source and those found in the literature. Calculating 1000 doses (individual voxel uncertainties of ∼0.05%) in a voxel grid Fano test for monoenergetic 500 keV electrons and 177 Lu electrons results in 94% and 99% of the doses being within 0.1% of the expected dose, respectively. For a hypothetical 177 Lu treatment, patient prostate, rectum, bone marrow, and bladder dose volume histograms (DVHs) results did not vary significantly when using the TL estimator and not modeling electron transport, modeling bone marrow explicitly (rather than using generic tissue compositions), and reducing activity to voxels containing partial or full calcifications to half or none, respectively. Dose profiles through different regions demonstrate there are some differences with model choices not seen in the DVH. Simulations using the TL estimator can be completed in under 15 min (∼30 min when using standard interaction scoring). CONCLUSION: This work shows egs_mird to be a reliable MC code for computing TRT doses as realistically as the patient Computed Tomography (CT) and Positron Emission Tomography (PET) data allow. Furthermore, the code can compute doses to sub-1% uncertainty within 15 min, with little to no optimization. Thus, this work supports the use of egs_mird for dose calculations in TRT.

On the Monte Carlo simulation of electron transport in the sub-1 keV energy range.

PURPOSE: The validity of "classic" Monte Carlo (MC) simulations of electron and positron transport at sub-1 keV energies is investigated in the context of quantum theory. METHODS: Quantum theory dictates that uncertainties on the position and energy-momentum four-vectors of radiation quanta obey Heisenberg's uncertainty relation; however, these uncertainties are neglected in "classical" MC simulations of radiation transport in which position and momentum are known precisely. Using the quantum uncertainty relation and electron mean free path, the magnitudes of uncertainties on electron position and momentum are calculated for different kinetic energies; a validity bound on the classical simulation of electron transport is derived. RESULTS: In order to satisfy the Heisenberg uncertainty principle, uncertainties of 5% must be assigned to position and momentum for 1 keV electrons in water; at 100 eV, these uncertainties are 17 to 20% and are even larger at lower energies. In gaseous media such as air, these uncertainties are much smaller (less than 1% for electrons with energy 20 eV or greater). CONCLUSIONS: The classical Monte Carlo transport treatment is questionable for sub-1 keV electrons in condensed water as uncertainties on position and momentum must be large (relative to electron momentum and mean free path) to satisfy the quantum uncertainty principle. Simulations which do not account for these uncertainties are not faithful representations of the physical processes, calling into question the results of MC track structure codes simulating sub-1 keV electron transport. Further, the large difference in the scale at which quantum effects are important in gaseous and condensed media suggests that track structure measurements in gases are not necessarily representative of track structure in condensed materials on a micrometer or a nanometer scale.

Comparison of dose calculation methods for brachytherapy of intraocular tumors.

PURPOSE: To investigate dosimetric differences among several clinical treatment planning systems (TPS) and Monte Carlo (MC) codes for brachytherapy of intraocular tumors using 125I or 103Pd plaques, and to evaluate the impact on the prescription dose of the adoption of MC codes and certain versions of a TPS (Plaque Simulator with optional modules). METHODS: Three clinical brachytherapy TPS capable of intraocular brachytherapy treatment planning and two MC codes were compared. The TPS investigated were Pinnacle v8.0dp1, BrachyVision v8.1, and Plaque Simulator v5.3.9, all of which use the AAPM TG-43 formalism in water. The Plaque Simulator software can also handle some correction factors from MC simulations. The MC codes used are MCNP5 v1.40 and BrachyDose/EGSnrc. Using these TPS and MC codes, three types of calculations were performed: homogeneous medium with point sources (for the TPS only, using the 1D TG-43 dose calculation formalism); homogeneous medium with line sources (TPS with 2D TG-43 dose calculation formalism and MC codes); and plaque heterogeneity-corrected line sources (Plaque Simulator with modified 2D TG-43 dose calculation formalism and MC codes). Comparisons were made of doses calculated at points-of-interest on the plaque central-axis and at off-axis points of clinical interest within a standardized model of the right eye. RESULTS: For the homogeneous water medium case, agreement was within approximately 2% for the point- and line-source models when comparing between TPS and between TPS and MC codes, respectively. For the heterogeneous medium case, dose differences (as calculated using the MC codes and Plaque Simulator) differ by up to 37% on the central-axis in comparison to the homogeneous water calculations. A prescription dose of 85 Gy at 5 mm depth based on calculations in a homogeneous medium delivers 76 Gy and 67 Gy for specific 125I and 103Pd sources, respectively, when accounting for COMS-plaque heterogeneities. For off-axis points-of-interest, dose differences approached factors of 7 and 12 at some positions for 125I and 103Pd, respectively. There was good agreement (approximately 3%) among MC codes and Plaque Simulator results when appropriate parameters calculated using MC codes were input into Plaque Simulator. Plaque Simulator and MC users are perhaps at risk of overdosing patients up to 20% if heterogeneity corrections are used and the prescribed dose is not modified appropriately. CONCLUSIONS: Agreement within 2% was observed among conventional brachytherapy TPS and MC codes for intraocular brachytherapy dose calculations in a homogeneous water environment. In general, the magnitude of dose errors incurred by ignoring the effect of the plaque backing and Silastic insert (i.e., by using the TG-43 approach) increased with distance from the plaque's central-axis. Considering the presence of material heterogeneities in a typical eye plaque, the best method in this study for dose calculations is a verified MC simulation.

High spatial resolution dosimetry with uncertainty analysis using Raman micro-spectroscopy readout of radiochromic films.

PURPOSE: The purpose of this work is to develop a new approach for high spatial resolution dosimetry based on Raman micro-spectroscopy scanning of radiochromic film (RCF). The goal is to generate dose calibration curves over an extended dose range from 0 to 50 Gy and with improved sensitivity to low (<2 Gy) doses, in addition to evaluating the uncertainties in dose estimation associated with the calibration curves. METHODS: Samples of RCF (EBT3) were irradiated at a broad dose range of 0.03-50 Gy using an Elekta Synergy clinical linear accelerator. Raman spectra were acquired with a custom-built Raman micro-spectroscopy setup involving a 500 mW, multimode 785 nm laser focused to a lateral spot diameter of 30 µm on the RCF. The depth of focus of 34 µm enabled the concurrent collection of Raman spectra from the RCF active layer and the polyester laminate. The preprocessed Raman spectra were normalized to the intensity of the 1614 cm-1 Raman peak from the polyester laminate that was unaltered by radiation. The mean intensities and the corresponding standard deviation of the active layer Raman peaks at 696, 1445, and 2060 cm-1 were determined for the 150 × 100 µm2 scan area per dose value. This was used to generate three calibration curves that enabled the conversion of the measured Raman intensity to dose values. The experimental, fitting, and total dose uncertainty was determined across the entire dose range for the dosimetry system of Raman micro-spectroscopy and RCF. RESULTS: In contrast to previous work that investigated the Raman response of RCFs using different methods, high resolution in the dose response of the RCF, even down to 0.03 Gy, was obtained in this study. The dynamic range of the calibration curves based on all three Raman peaks in the RCF extended up to 50 Gy with no saturation. At a spatial resolution of 30 × 30 µm2 , the total uncertainty in estimating dose in the 0.5-50 Gy dose range was [6-9]% for all three Raman calibration curves. This consisted of the experimental uncertainty of [5-8]%, and the fitting uncertainty of [2.5-4.5]%. The main contribution to the experimental uncertainty was determined to be from the scan area inhomogeneity which can be readily reduced in future experiments. The fitting uncertainty could be reduced by performing Raman measurements on RCF samples at further intermediate dose values in the high and low dose range. CONCLUSIONS: The high spatial resolution experimental dosimetry technique based on Raman micro-spectroscopy and RCF presented here, could become potentially useful for applications in microdosimetry to produce meaningful dose estimates in cellular targets, as well as for applications based on small field dosimetry that involve high dose gradients.

Update of the CLRP eye plaque brachytherapy database for photon-emitting sources.

PURPOSE: To update and extend the Carleton Laboratory for Radiotherapy Physics (CLRP) Eye Plaque (EP) dosimetry database for low-energy photon-emitting brachytherapy sources using egs_brachy, an open-source EGSnrc application. The previous database, CLRP_EPv1, contained datasets for the Collaborative Ocular Melanoma Study (COMS) plaques (10-22 mm diameter) with 103 Pd or 125 I seeds (BrachyDose-computed, 2008). The new database, CLRP_EPv2, consists of newly calculated three-dimensional (3D) dose distributions for 17 plaques [eight COMS, five Eckert & Ziegler BEBIG, and four others representative of models used worldwide] for 103 Pd, 125 I, and 131 Cs seeds. ACQUISITION AND VALIDATION METHODS: Plaque models are developed with egs_brachy, based on published/manufacturer dimensions and material data. The BEBIG plaques (modeled for the first time) are identical in dimensions to COMS plaques but differ in elemental composition and/or density. Previously benchmarked seed models are used. Eye plaques and seeds are simulated at the center of full-scatter water phantoms, scoring in (0.05 cm)3 voxels spanning the eye for scenarios: (a) "HOMO": simulated TG43 conditions; (b) "HETERO": eye plaques and seeds fully modeled; (c) "HETsi" (BEBIG only): one seed is active at a time with other seed geometries present but not emitting photons (inactive); summation over all i seeds in a plaque then yields "HETsum" (includes interseed effects). For validation, doses are compared to those from CLRP_EPv1 and published data. DATA FORMAT AND ACCESS: Data are available at https://physics.carleton.ca/clrp/eye_plaque_v2, http://doi.org/10.22215/clrp/EPv2. The data consist of 3D dose distributions (text-based EGSnrc "3ddose" file format) and graphical presentations of the comparisons to previously published data. POTENTIAL APPLICATIONS: The CLRP_EPv2 database provides accurate reference 3D dose distributions to advance ocular brachytherapy dose evaluations. The fully-benchmarked eye plaque models will be freely distributed with egs_brachy, supporting adoption of model-based dose evaluations as recommended by TG-129, TG-186, and TG-221.

Dosimetric investigation of 103Pd permanent breast seed implant brachytherapy based on Monte Carlo calculations.

PURPOSE: Permanent breast seed implant using 103Pd is emerging as an effective adjuvant radiation technique for early stage breast cancer. However, clinical dose evaluations follow the water-based TG-43 approach with its considerable approximations. Toward clinical adoption of advanced TG-186 model-based dose evaluations, this study presents a comprehensive investigation for permanent breast seed implant considering both target and normal tissue doses. METHODS AND MATERIALS: Dose calculations are performed with the free open-source Monte Carlo (MC) code, egs_brachy, using two types of virtual patient models: TG43sim (simulated TG-43 conditions) and MCref (heterogeneous tissue modeling from patient CT, seeds at implant angle) for 35 patients. The sensitivity of dose metrics to seed orientation and tissue segmentation are assessed. RESULTS: In the target volume, D90 is 14.1 ± 5.8% lower with MCref than with TG43sim, on average. Conversely, normal tissue doses are generally higher with MCref than with TG43sim, for example, by 22 ± 13% for skin D1cm2, 82 ± 7% for ribs Dmax, and 71 ± 23% for heart D1cm3. Discrepancies between MCref and TG43sim doses vary over the patient cohort, as well as with the tissue and metric considered. Skin doses are particularly sensitive to seed orientation, with average difference of 4% (maximum 28%) in D1cm2 for seeds modeled vertically (egs_brachy default) compared with those aligned with implant angle. CONCLUSIONS: TG-43 dose evaluations generally underestimate doses to critical normal organs/tissues while overestimating target doses. There is considerable variation in MCref and TG43sim on a patient-by-patient basis, motivating clinical adoption of patient-specific MC dose calculations. The MCref framework presented herein provides a consistent modeling approach for clinical implementation of advanced TG-186 dose calculations.